Traditional treatment for type 1 diabetes mellitus （T1DM） primarily involves insulin replacement， yet some patients encounter issues such as significant blood glucose fluctuations， high risk of hypoglycemia， and weight gain. In recent years， the adjuvant therapeutic role of non-insulin hypoglycemic drugs in T1DM has gradually gained attention. This article reviews the mechanisms of action and clinical research progress of five types of non-insulin hypoglycemic drugs in the treatment of T1DM： amylin analogues （pramlintide）， biguanides （metformin）， sodium-glucose co-transporter 2 inhibitor， dipeptidyl peptidase-4 inhibitor， and glucagon-like peptide-1 receptor agonist. It is found that these drugs can enhance clinical benefits for T1DM patients by improving insulin sensitivity， delaying gastric emptying， promoting urinary glucose excretion， and regulating incretin levels， thereby reducing glycated hemoglobin levels， decreasing insulin dosage， and managing body weight. Simultaneously， these drugs also present limitations such as low patient compliance due to complex dosing regimens， increased risk of diabetic ketoacidosis， and heterogeneity in glycemic control. Future research could focus on developing individualized treatment strategies， combining pharmacogenomics with novel biomarkers to precisely identify subpopulations of patients who may benefit， and delving into the potential value of these drugs in delaying diabetic vascular complications and improving patients’ quality of life.

ObjectiveTo explore the effect of piercing electroacupuncture on ankle muscle strength, dynamic balance and subjective stability in patients with functional ankle instability (FAI). MethodsA total of 48 patients with FAI admitted to the Affiliated Hospital of Traditional Chinese Medicine, Shandong Second Medical University from April, 2024 to July, 2025 were enrolled and randomly divided into control group (n = 24) and experimental group (n = 24). The control group received multimodal functional training, while the experimental group received piercing electroacupuncture in addition, for six weeks. Relative peak torque of ankle plantarflexion, dorsiflexion, inversion and eversion were measured with isokinetic muscle strength testing system before and after treatment, while Y-Balance Test (YBT) and Cumberland Ankle Instability Tool (CAIT) were adopted for evaluation. ResultsOne case dropped out in each group. Relative peak torque of ankle plantarflexion, dorsiflexion, inversion and eversion at each angular velocity, the normalized distance in each direction and composite score of YBT, as well as the score of CAIT increased in both groups after treatment (|t| > 2.891, P < 0.01), while all the indicators were better in the experimental group than in the control group (|t| > 2.104, P < 0.05), except dorsiflexion muscle strength. ConclusionCombination of piercing electroacupuncture can further improve perimalleolar muscle strength, dynamic balance and subjective stability in patients with FAI.

Objective To explore the wearing status and actual noise reduction effect of hearing protectors among noise workers in a typical automobile manufacturing enterprise. Methods In April 2024, an occupational hazard factor testing was carried out in an automobile manufacturing industry, and at the same time, the hearing protection fit test was conducted for noise workers. Intervention and guidance were provided to those who did not pass the minimum standard of baseline PAR. The difference in PAR between baseline and post-intervention was compared, and the effectiveness of hearing protector wearing method training was evaluated. Results The exceeding rate of the company's noise operation post was 50.77% (66/130). The baseline PAR of the subjects with working experience of less than 15 years and wearing hearing protectors throughout noisy work was higher, and the differences were statistically significant (P<0.05). Compared with those with 80dB≤L_{EX, 8h}<85dB, more research subjects with L_{EX, 8h}≥85dB failed baseline PAR (39.13%). After intervention, the PAR of the subjects who did not pass the minimum standard of baseline PRA increased from 2.0 (0.0, 5.3) to 17.0 (14.8, 20.0), and the protection level was significantly improved, and the difference was statistically significant (P<0.01). Conclusion The individual fit test of hearing protector is an important means to evaluate the actual noise reduction level of hearing protector and guide the selection of hearing protection models. Corporate training can help improve the PAR of hearing protectors.

To analyze the distribution of serotypes and antimicrobial resistance of clinical Salmonella isolates from multiple centers across China.

Objective To investigate the diagnostic value of color Doppler ultrasound of neck vessels combined with head and neck CT angiography (CTA) in detecting carotid artery stenosis among patients with stroke. Methods A total of 104 patients with stroke admitted to the hospital between January 2023 and November 2024 were enrolled. All patients underwent color Doppler ultrasound of neck vessels and head and neck CTA, with digital subtraction angiography (DSA) used as the gold standard. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic performance of each modality alone and in combination for detecting carotid artery stenosis in patients with stroke. Results According to the DSA results, among the 104 patients, 7 were normal, while 47, 16, 25, and 9 cases showed mild, moderate, and severe stenosis and occlusion, respectively. Color Doppler ultrasound results showed 6 normal cases, and 45, 20, 23, and 10 cases of mild, moderate, and severe stenosis and occlusion, respectively. Using DSA as the gold standard, the sensitivity, specificity and kappa value for diagnosing carotid artery stenosis were 98.97%, 85.71% and 0.848, respectively. Head and neck CTA results showed 5 normal cases, and 47, 19, 22, and 9 cases of mild, moderate, and severe stenosis and occlusion, respectively. The sensitivity, specificity and kappa value of head and neck CTA for diagnosing carotid artery stenosis were 100.00%, 71.43% and 0.823, respectively. The combined examination results showed that among the 104 patients, there were 7 normal cases, and 46, 18, 24, and 9 cases of mild, moderate, and severe stenosis and occlusion, respectively. The sensitivity, specificity and kappa value of the combined diagnosis were 100.00%, 100.00% and 1.000, respectively. In the ROC analysis, the areas under the curves of color Doppler ultrasound, head and neck CTA, and the combined method were 0.968, 0.934, and 1.000, respectively, with no significant difference among the three ROC curves (Z = 1.017, 0.994, 1.527, respectively, P = 0.309, 0.320, 0.167, respectively). Conclusion Color Doppler ultrasound of neck vessels combined with head and neck CTA shows good consistency with DSA in diagnosing carotid artery stenosis and its severity among patients with stroke. This combined method demonstrates high diagnostic performance, making it worthy of clinical application and promotion.

ObjectiveTo investigate the possible mechanism of Shufeng Jiedu capsules （SFJD） in alleviating influenza A （H1N1） virus pneumonia and focus on its effect on Toll-like receptor （TLR） signaling pathway in respiratory epithelial cells. MethodsA mouse model of viral pneumonia was established via the A/PR/8/34 （PR8） strain of influenza A virus. Mice were randomly divided into a normal group， a PR8 infection （PR8） group， and an SFJD group （8.4 g·kg^-1）， with 10 mice in each group. The day of infection was designated as day 1. The SFJD group was administered intragastrically at a volume of 20 mL·kg^-1 daily， while the normal and PR8 groups were given an equal volume of deionized water. Micro-computed tomography （Micro-CT） was performed on day 5， and the mice were dissected to collect their lungs， after which the lung index was calculated to verify the therapeutic effect of SFJD. Single-cell sequencing was used to analyze the differentially expressed genes in respiratory epithelial cells. Multiplex fluorescence immunohistochemistry was employed to detect the expression of TLR， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） proteins in epithelial cell adhesion molecule （EpCAM）-positive cells， and the proportion of respiratory epithelial cells expressing TLR pathway proteins was calculated. Respiratory epithelial cells were then sorted by flow cytometry， and Western blot was used to detect the expression of TLR， MyD88， TRAF6， Toll-interleukin receptor domain-containing adaptor inducing interferon-β （TRIF）， inhibitor of κB kinase α （IKKα）， and nuclear factor-κB （NF-κB） in the sorted epithelial cells. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in lung tissue. ResultsAt the transcriptional level， SFJD reversed the expression of TLR signaling pathway genes in respiratory epithelial cells， downregulating multiple TLR signaling pathway-related genes （P<0.01）. At the protein level， SFJD significantly reduced the proportion of respiratory epithelial cells expressing TLR3 （P<0.05）， the expression levels of TLR2， TLR3， TLR4， TRIF， TRAF6， IKKα， and NF-κB in epithelial cells（P<0.05， P<0.01）， as well as the levels of pro-inflammatory cytokines IL-1β and TNF-α in lung tissue （P<0.01）. ConclusionSFJD may alleviate viral pneumonia by suppressing the expression of TLR in respiratory epithelial cells and their subsequent signaling cascades.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer with a high mortality rate in its late stages. One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor (EGFR) inhibitors. Therefore, it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy. METHODS: To evaluate the efficacy of the combination of the Ca 2+ /calmodulin-dependent protein kinase II (CAMK2) inhibitor KN93 and EGFR inhibitors, we performed in vitro and in vivo experiments using two FAT atypical cadherin 1 ( FAT1 )-deficient (SCC9 and SCC25) and two FAT1 wild-type (SCC47 and HN12) OSCC cell lines. We assessed the effects of EGFR inhibitors (afatinib or cetuximab), KN93, or their combination on the malignant phenotype of OSCC in vivo and in vitro . The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2 (SOX2) were analyzed. Changes in the yes-associated protein 1 (YAP1) protein were characterized. Moreover, we analyzed mitochondrial dysfunction. Besides, the effects of combination therapy on mitochondrial dynamics were also evaluated. RESULTS: OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment. The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation, survival, and migration of FAT1 -mutated OSCC cells and suppressed tumor growth in vivo . Mechanistically, combination therapy enhanced the therapeutic sensitivity of FAT1 -mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins. Furthermore, combination therapy induced reactive oxygen species (ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics, ultimately resulting in tumor suppression. CONCLUSION Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.
Humans ; ErbB Receptors/metabolism* ; Mouth Neoplasms/metabolism* ; Cell Line, Tumor ; Animals ; Drug Resistance, Neoplasm/genetics* ; Cadherins/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Mice ; Mutation/genetics* ; Mice, Nude ; Protein Kinase Inhibitors/therapeutic use* ; Cetuximab/pharmacology* ; Afatinib/therapeutic use* ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects*

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Rheumatoid arthritis (RA) is a common systemic inflammatory autoimmune disease characterized by synovitis and bone destruction. Its clinical characteristics are mainly joint pain, swelling, stiffness and joint deformity. Due to the poor efficacy of both drug and non-drug therapies, RA can significantly impact patients' quality of life and increase personal and socioeconomic burdens. Studies have found that the Janus kinase (JAK)/signal transduction and activator of transcription (STAT) pathway, as classical intracellular signaling pathway, plays an important role in the occurrence and development of connective tissue diseases by regulating inflammation, immunity, and cell differentiation. This article reviews the research progress on the involvement of JAK/STAT signaling pathway in the mechanism of RA pathological pain, in order to provide some reference for understanding the pathogenesis of RA pathological pain and developing specific drug.
Arthritis, Rheumatoid/metabolism* ; Humans ; Signal Transduction/physiology* ; Janus Kinases/metabolism* ; STAT Transcription Factors/metabolism* ; Pain/etiology* ; Animals

This study identified 8 members including NjBIN2 of the GSK3 family in Nardostachys jatamansi by bioinformatics analysis. Moreover, the phylogenetic tree revealed that the GKS3 family members of N. jatamansi had a close relationship with those of Arabidopsis. RT-qPCR results showed that NjBIN2 presented a tissue-specific expression pattern with the highest expression in roots, suggesting that NjBIN2 played a role in root growth and development. In addition, the application of epibrassinolide or the brassinosteroid(BR) synthesis inhibitor(brassinazole) altered the expression pattern of NjBIN2 and influenced the photomorphogenesis(cotyledon opening) and root development of N. jatamansi, which provided direct evidence about the functions of NjBIN2. In conclusion, this study highlights the roles of BIN2 in regulating the growth and development of N. jatamansi by analyzing the expression pattern and biological function of NjBIN2. It not only enriches the understanding about the regulatory mechanism of the growth and development of N. jatamansi but also provides a theoretical basis and potential gene targets for molecular breeding of N. jatamansi with improved quality in the future.
Brassinosteroids/metabolism* ; Steroids, Heterocyclic/metabolism* ; Gene Expression Regulation, Plant/drug effects* ; Plant Proteins/metabolism* ; Phylogeny ; Nardostachys/metabolism* ; Plant Growth Regulators/pharmacology* ; Plant Roots/drug effects*